This project requests support for an experimental investigation on the nature and mechanisms of frameshift mutagenesis by mutagens and carcinogens capable of covalent reaction with DNA. The proposed series of experiments seeks to determine the in vivo fate of two kinds of chemically reacted DNA molecules: 1) intact pBR 322 plasmids with frameshifts introduced at selected restriction sites and 2) short DNA fragments (decamers to dodecamers) which can be inverted at selected sites. These approaches should permit us to establish the statistical frequencies of frameshift mutagenesis as well as detailed sequence changes induced by specific mutagens or carcinogens.